This invention relates to polypeptides and vaccines and conjugates therefrom as well as to methods for controlling streptococcal infection.
The M protein of group A streptococci is a fibrous dimer of helices arranged in a coiled coil extending about 50 nm from the surface of these organisms. It is a filbrillar molecule of which there exists more than 80 serological types. M protein renders the streptococcus resistant to nonimmune phagocytosis. It is the major virulence factor of streptococcal bacteria.
It has now been surprisingly found that polypeptides from the conserved region of the M protein elicit a protective immune response when administered to a mammal in need of protection against streptococcal infection.
The present invention thus provides a polypeptide which elicits an immune response in a mammal on administration to said mammal which comprises an amino acid sequence containing at least 5 amino acid residues, said sequence being the same or substantially the same as a sequence of amino acid residues in the conserved exposed region of the M protein of group A streptococci.
The present invention also provides an antigen conjugate which elicits an immune response in a mammal on administration to said mammal which comprises a linkable carrier covalently linked to a polypeptide which comprises an amino acid sequence containing at least 5 amino acid residues, said sequence being the same or substantially the same as a sequence of amino acid residues in the conserved exposed region of the M protein of group A streptococci.
The present invention further provides a method of controlling streptococcal infection in a mammal in need of such control which comprises intranasal or oral administration to said mammal of a polypeptide which comprises an amino acid sequence containing at least 5 amino acid residues said sequence being the same or substantially the same as a sequence of amino acid residues in the conserved exposed region of the M protein of group A streptococci in an amount which is sufficient to stimulate the production of a streptococcal infection controlling quantity of immunoglobulin.
In addition, the present invention provides a vaccine to protect against streptococcal infection which comprises a biologically acceptable diluent and a polypeptide, said polypeptide comprising an amino acid sequence containing at least 5 amino acid residues, said sequence being the same or substantially the same as a sequence of amino acid residues in the conserved exposed region of the M protein of group A streptococci said polypeptide being present in an amount which is sufficient to stimulate the production of sufficient immunoglobulin to elicit such protection.
Furthermore, the present invention provides certain polypeptides comprising specific sequences from the conserved exposed region of the M protein of group A streptococci.
The term xe2x80x9cthe same or substantially the samexe2x80x9d is used herein to describe the sequence of amino acids in the polypeptides having the desirable activity because such polypeptides are either identical to a segment from the exposed conserved region of the M protein of group A streptococci or so similar to the segment that it has the same activity. No undue experimentation is required to determine polypeptides which are so similar to a segment from the exposed conserved region of the M protein that they have the same activity as those which are the same as the segment. The skilled artisan, from reading this specification can prepare homologous polypeptides having the same activity and substantially the same sequence as a segment from the exposed conserved region of the M protein. For instance, the termini may be extended, e.g., to provide an anchor to bind the polypeptide to a binder or carrier molecule. A polypeptide with the same activity and a high degree of homology with a sequence from the conserved, exposed region might be synthesized more readily or be less expensive to prepare, and, this polypeptide is considered within the scope of this invention. The exact sequence of the M protein segment is not essential to the practice of this invention so long as it has the desired activity.
To similarly clarify the terms used herein, the polypeptides of the present invention are not the entire M protein, but rather, have the same, or substantially the same amino acid sequence as a segment from the conserved, exposed region of the M protein of group A streptococci. The polypeptides of this invention are not considered to be naturally occurring. To obtain the polypeptides of this invention, selective enzymatic or chemical cleavage from the M protein can be employed, although synthesis, e.g., solid phase synthesis, is preferred. Thus, the polypeptides employed in this invention are not naturally occurring polypeptides because, even if isolated from the M protein, they are pure or substantially pure polypeptides or are purer than the M protein. In any event, the polypeptides herein, even if isolated from the M protein, are not products of nature because the polypeptides herein are not the entire M protein, but are the same or substantially the same as an amino acid sequence from a segment of the M protein, the conserved exposed region.
Furthermore, as detailed below, the polypeptides of this invention do not have the same characteristics and utility as any M protein or other naturally occurring protein, because the native M protein cannot be utilized to protect against streptococcal infections by different streptococcal zenotypes because of species variability of the M protein found in different strains of streptococci, whereas the polypeptides of this invention can be used to prepare vaccines affording broad protection which is not strain specific. Thus, the polypeptides of this invention are not products of nature as they do not exist as distinct entities of nature and have never before been produced, and because no product of nature has the same properties as these polypeptides.